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1.
Surg Endosc ; 38(8): 4571-4582, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38951238

RESUMO

BACKGROUND: Adrenalectomy for pheochromocytoma (PHEO) is challenging because of the high risk of intraoperative hemodynamic instability (HDI). This study aimed to compare the incidence and risk factors of intraoperative HDI between laparoscopic left adrenalectomy (LLA) and laparoscopic right adrenalectomy (LRA). METHODS: We retrospectively analyzed two hundred and seventy-one patients aged > 18 years with unilateral benign PHEO of any size who underwent transperitoneal laparoscopic adrenalectomy at our hospitals between September 2016 and September 2023. Patients were divided into LRA (N = 122) and LLA (N = 149) groups. Univariate and multivariate logistic regression analyses were used to predict intraoperative HDI. In multivariate analysis for the prediction of HDI, right-sided PHEO, PHEO size, preoperative comorbidities, and preoperative systolic blood pressure were included. RESULTS: Intraoperative HDI was significantly higher in the LRA group than in the LLA (27% vs. 9.4%, p < 0.001). In the multivariate regression analysis, right-sided tumours showed a higher risk of intraoperative HDI (odds ratio [OR] 5.625, 95% confidence interval [CI], 1.147-27.577, p = 0.033). The tumor size (OR 11.019, 95% CI 3.996-30.38, p < 0.001), presence of preoperative comorbidities [diabetes mellitus, hypertension, and coronary heart disease] (OR 7.918, 95% CI 1.323-47.412, p = 0.023), and preoperative systolic blood pressure (OR 1.265, 95% CI 1.07-1.495, p = 0.006) were associated with a higher risk of HDI in both LRA and LLA, with no superiority of one side over the other. CONCLUSION: LRA was associated with a significantly higher intraoperative HDI than LLA. Right-sided PHEO was a risk factor for intraoperative HDI.


Assuntos
Neoplasias das Glândulas Suprarrenais , Adrenalectomia , Hemodinâmica , Complicações Intraoperatórias , Laparoscopia , Feocromocitoma , Humanos , Feocromocitoma/cirurgia , Adrenalectomia/métodos , Adrenalectomia/efeitos adversos , Laparoscopia/métodos , Laparoscopia/efeitos adversos , Neoplasias das Glândulas Suprarrenais/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Complicações Intraoperatórias/epidemiologia , Complicações Intraoperatórias/etiologia , Fatores de Risco , Idoso
2.
Parasitol Res ; 123(6): 256, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38935203

RESUMO

Cutaneous leishmaniasis (CL), a neglected tropical disease, is a major public health concern in Yemen, with Leishmania tropica identified as the main causative agent. This study aims to investigate the occurrence and distribution of Leishmania parasites in domestic and wild animals in CL endemic areas in the western highlands of Yemen. A cross-sectional study was conducted in the Utmah District of western Yemen. Blood and skin scraping specimens were collected from 122 domestic and wild animals and tested for the Leishmania DNA using internal transcribed spacer 1 (ITS1) nested polymerase chain reaction. Phylogenetic analyses were performed on 20 L. tropica sequences obtained from animals in this study and 34 sequences from human isolates (collected concurrently from the same study area) retrieved from the GenBank. Overall, L. tropica was detected in 16.4% (20/122) of the examined animals, including 11 goats, two dogs, two bulls, one cow, one donkey, one rabbit, one rat and one bat. None of the examined cats and sheep was positive. The animal sequences were segregated into four different L. tropica haplotypes, with the majority of the animal (15/20) and human (32/34) sequences composed of one dominant haplotype/genotype. These findings represent the first confirmed evidence of natural L. tropica infections in different kinds of domestic and wild animals in western Yemen, suggesting these animals potentially have a role in the transmission of CL in Yemen. Therefore, a One Health approach is required for the effective prevention and control of this devastating disease among endemic populations.


Assuntos
Animais Domésticos , Animais Selvagens , Leishmania tropica , Leishmaniose Cutânea , Saúde Única , Filogenia , Animais , Leishmania tropica/genética , Leishmania tropica/isolamento & purificação , Leishmania tropica/classificação , Leishmaniose Cutânea/epidemiologia , Leishmaniose Cutânea/veterinária , Leishmaniose Cutânea/parasitologia , Iêmen/epidemiologia , Humanos , Estudos Transversais , Animais Selvagens/parasitologia , Animais Domésticos/parasitologia , DNA de Protozoário/genética , Doenças Negligenciadas/parasitologia , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/veterinária , Doenças Endêmicas/veterinária , DNA Espaçador Ribossômico/genética , Reação em Cadeia da Polimerase/veterinária , Análise de Sequência de DNA , Masculino
3.
Andrologia ; 54(1): e14308, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34773422

RESUMO

This study aimed to screen healthy individuals who contracted COVID-19 for erectile dysfunction (ED) and to determine the potential risk factors that can predict ED in these individuals. One hundred and seven cases versus 90 controls agreed to participate in the study. Two structured interviews with 1 month interval were conducted. All participants were evaluated by the validated Arabic version of the international index of erectile function (IIEF-5) and assessment of the psychological state by Hamilton depression rating scale (HDRS). Interestingly, the study had demonstrated a significant difference in mean testosterone level between cases and controls (3.91 ± 2.31, 5.04 ± 2.22, p < 0.001 respectively). Additionally, the study had demonstrated a significant difference in mean IIEF-5 score between cases and controls (22.63 ± 2.79, 23.54 ± 1.26, p < 0.041 respectively). Moreover, there were significant differences in mean anxiety and stress scores of the cases before and after COVID-19 (4.95 ± 4.03, 6.19 ± 3.55, p = 0.022, 12.75 ± 9.98, 15.30 ± 7.42, p = 0.024 respectively). A multiple logistic regression model for predicting ED occurrence post-COVID-19 had revealed that smoking, baseline IIEF-5 score and COVID-19 severity (p = 0.022, p = 0.017, p = 0.021, p = 0.009, p = 0.008 respectively) were the only significant independent variables.


Assuntos
COVID-19 , Disfunção Erétil , Estudos de Casos e Controles , Egito/epidemiologia , Disfunção Erétil/epidemiologia , Disfunção Erétil/etiologia , Humanos , Masculino , SARS-CoV-2
4.
Bioorg Med Chem Lett ; 54: 128443, 2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34763081

RESUMO

Here we report the first small-molecule inhibitors of human sulfide:quinone oxidoreductase (SQOR) that decrease the rate of breakdown of hydrogen sulfide (H2S), a potent cardioprotective signaling molecule. SQOR is a mitochondrial membrane-bound protein that catalyzes a two-electron oxidation of H2S to sulfane sulfur (S0), using glutathione (or sulfite) and coenzyme Q (CoQ) as S0 and electron acceptor, respectively. Inhibition of SQOR may constitute a new approach for the treatment of heart failure with reduced ejection fraction. Starting from top hits identified in a high-throughput screen, we conducted SAR development guided by docking of lead candidates into our crystal structure of SQOR. We identified potent SQOR inhibitors such as 19 which has an IC50 of 29 nM for SQOR inhibition and favorable pharmacokinetic and ADME properties required for in vivo efficacy testing.


Assuntos
Inibidores Enzimáticos/farmacologia , Hidrocarbonetos Aromáticos/farmacologia , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/antagonistas & inibidores , Bibliotecas de Moléculas Pequenas/farmacologia , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Hidrocarbonetos Aromáticos/síntese química , Hidrocarbonetos Aromáticos/química , Estrutura Molecular , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/metabolismo , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/química , Relação Estrutura-Atividade
5.
Egypt Heart J ; 76(1): 94, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39060876

RESUMO

BACKGROUND: Cardiogenic shock (CS) remains a major cause of morbidity and mortality, particularly in developing countries where there are limited resources and a lack of data on CS outcomes. This study aimed to investigate 30-day all-cause mortality in Egyptian patients with CS at tertiary referral centers. RESULTS: This prospective, observational multicenter registry analyzed 16,681 patients from six cardiac centers, to evaluate the incidence, causes and predictors of CS-related mortality. Among the 529 diagnosed CS patients, 68.2% had an ischemic etiology. No discernable variations were observed in clinical or laboratory features, as well as mortality rates, between ischemic and non-ischemic CS patients. Within 30 days, 210 deaths (39.7%) occurred. Non-survivors with ischemic CS had a higher prevalence of diabetes, worsening renal function, and were more likely to receive multiple inotropes. Mortality did not significantly differ between acute coronary syndrome patients with ST elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) (42.7% vs. 43.7%, p < 0.887). However, anterior STEMI patients had significantly higher mortality than those with inferior STEMI (49.5% vs. 21.6%, p < 0.003). Multivariate regression analysis identified predictors of mortality in CS, including the median hospital stay duration, leucocyte count, alanine transaminase levels, highest creatinine levels, resuscitated cardiac arrest, and use of norepinephrine, epinephrine, and dopamine. CONCLUSION: In an Egyptian cohort, CS incidence was 3.17%, with no mortality difference based on the underlying etiology. Independent predictors of 30-day all-cause mortality included worsening renal function, leucocyte count, resuscitated cardiac arrest, and use of multiple inotropes/vasopressors.

6.
Dent Med Probl ; 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39115543

RESUMO

BACKGROUND: The durability of indirect restorations is significantly influenced by marginal adaptation and internal fit. The use of computer-aided design/computer-aided manufacturing (CAD/CAM) with digital impressions has reduced dental prosthesis fabrication errors, improving the long-term survivability of the restorations. OBJECTIVES: The present study assessed the impact of intraoral and extraoral scanning methods on the marginal adaptation and internal fit of 2 different types of monolithic crowns manufactured using CAD/CAM. MATERIAL AND METHODS: A total of 40 three-dimensional (3D) resin-printed dies were randomly assigned to 2 groups based on the type of crown material (n = 20 per group). Each group was divided into 2 subgroups (n = 10 per group) according to the die-scanning technique: subgroup A, scanned using the intraoral scanner (IOS) Primescan; and subgroup B, scanned using the extraoral scanner (EOS) inEos X5. The digitized photos were converted into a 3D virtual crown design using CAD software. The internal discrepancy values, and the marginal gap between the 3D resin-printed die and the crown were assessed using a ×50 digital microscope. The data was checked for normality with the Kolmogorov-Smirnov test, and the Mann-Whitney U test was used to compare the tested groups. The collected data was analyzed at a significance level set at p < 0.05. RESULTS: The different scanning techniques used had a statistically significant effect on the vertical marginal gap and the internal fit [µm] (p < 0.05). As far as the crown materials are concerned, BRILLIANT Crios showed a significantly higher marginal gap as compared to Tetric CAD when scanned with inEos X5 (p = 0.004), whereas the differences were insignificant with regard to the internal fit (p > 0.05).The crown parameters tested with both scanning systems were within the clinically acceptable ranges. CONCLUSIONS: Scanning methods and crown materials had an impact on the internal fit and vertical marginal gap of monolithic crowns.

7.
Pharm Dev Technol ; 18(5): 1238-46, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22582904

RESUMO

Press-coated sustained release tablets offer a valuable, cheap and easy manufacture alternative to the highly expensive, multi-step manufacture and filling of coated beads. In this study, propranolol HCl press-coated tablets were prepared using hydroxylpropylmethylcellulose (HPMC) as tablet coating material together with carbopol 971P and compressol as release modifiers. The prepared formulations were optimized for zero-order release using artificial neural network program (INForm, Intelligensys Ltd, North Yorkshire, UK). Typical zero-order release kinetics with extended release profile for more than 12 h was obtained. The most important variables considered by the program in optimizing formulations were type and proportion of polymer mixture in the coat layer and distribution ratio of drug between core and coat. The key elements found were; incorporation of 31-38 % of the drug in the coat, fixing the amount of polymer in coat to be not less than 50 % of coat layer. Optimum zero-order release kinetics (linear regression r2 = 0.997 and Peppas model n value > 0.80) were obtained when 2.5-10 % carbopol and 25-42.5% compressol were incorporated into the 50 % HPMC coat layer.


Assuntos
Propranolol/química , Acrilatos/química , Química Farmacêutica/métodos , Preparações de Ação Retardada/química , Cinética , Metilcelulose/química , Polímeros/química , Propranolol/administração & dosagem , Comprimidos/química
8.
Arch Ital Urol Androl ; 95(3): 11462, 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37668553

RESUMO

INTRODUCTION: Galectin-1 (Gal-1) and galectin-3 (Gal-3) are expressed by many immune cells and receive considerable attention in the context of immunity. We aimed to compare between seminal plasma and serum levels of Gal-1 and Gal-3 in azoospermic patients and fertile men. MATERIALS AND METHODS: This cross-sectional study was conducted at the andrology outpatient clinic from January (2022) to September (2022). A total of 90 participants were enrolled and divided into two equal groups: azoospermic and normal group. Semen analysis was done for all participants. Hormonal profile including FSH, LH, serum prolactin, total testosterone and estradiol was performed as well as assessment of serum and seminal levels of Gal-1 and Gal-3 by ELISA commercial kits. Finally, scrotal Duplex was done in standing and supine position. RESULTS: Serum and seminal levels of Gal-1 and Gal-3 were statistically significant higher in azoospermic patients compared with normal individuals (p < 0.001 for all). In addition, in healthy individuals there were statistically significant positive correlations between serum levels of Gal-1 and age, FSH, LH levels (r = 0.296, p = 0.005; r = 0.333, p = < 0.001; r = 0.312, p = 0.003, respectively) and serum levels of Gal-2 and FSH and LH (r = 0.436, p < 0.001; r = 0.350, p < 0.001, respectively), whereas serum Gal-3 showed a borderline positive correlation with age (r = 0.2, p = 0.059). Additionally, statistically significant positive correlations between seminal levels of Gal-1 and Gal-3 and free testosterone in healthy individuals were reported (r = 0.205, p = 0.053; r = 0.219, p = 0.038, respectively). On the other hand, there were negative correlations between serum and seminal levels of Gal-1 and Gal-3, total and progressive sperm motility, sperm count and abnormal sperm forms in healthy individuals (r = -0.382, p < 0.001; r = -0.405, p < 0.001; r = -0.376, p < 0.001; r = -0.364, p < 0.001) (r = -0.394, p < 0.001; r = -0.467, p < 0.001; r = -0.413, p < 0.001; r = -0.433, p < 0.001); (r = -0.372, p < 0.001; r = -0.377, p < 0.001; r = -0.317, p = 0.002; r = -0.311, p = 0.003)(r = -0.445, p < 0.001; r = -0.498, p < 0.001; r = -0.453, p < 0.001; r = -0.463, p < 0.001, respectively). Furthermore, statistically significant positive correlations between serum levels of Gal-1 and Gal-3 and age in azoospermic patients were reported (r = 0.511, p < 0.001; r = 0.390, p = 0.008, respectively). On the other hand, there were negative correlations between seminal Gal-1 and estradiol (E2) and seminal Gal-3 and FSH and LH in azoospermic patients (r= -0.318, p = 0.033; r = -0.322, p = 0.031; r = -0.477, p < 0.001, respectively). Also, negative correlations between serum Gal-3 and total and free testosterone in azoospermic patients were detected (r = -0.396, p = 0.007; r = -0.375, p = 0.011, respectively). CONCLUSIONS: Elevated serum and seminal levels of Gal-1 and Gal-3 have detrimental effects on spermatogenesis. Furthermore, the current study demonstrated potential regulatory effects of reproductive hormones on Gal-1 and Gal-3. Thus, future studies are needed to confirm such findings.


Assuntos
Azoospermia , Sêmen , Humanos , Masculino , Galectina 3 , Estudos Transversais , Hormônio Luteinizante , Hormônio Foliculoestimulante , Galectina 1 , Motilidade dos Espermatozoides , Testosterona , Estradiol
9.
Basic Clin Androl ; 33(1): 34, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38049720

RESUMO

BACKGROUND: Premature ejaculation (PE) is considered to be the most common male sexual disorder affecting 20% to 66% of sexually active men. Most of the patients had already tried on demand dapoxitine with no improvement. We aimed in the current study to assert the efficacy and safety profile of daily intake of 30 mg duloxetine in treating patients with lifelong premature ejaculation (LPE) as well as patients with acquired premature ejaculation (APE). RESULTS: The current study showed significant improvement in intravaginal ejaculatory latency time (IELT) after intake of duloxetine. All participants had a median Arabic index of premature ejaculation (AIPE) of 26, median IELT of 180 s, median male sexual quality of life (SQOL) of 43 after being treated with duloxetine (p value < 0.001 for all). While median AIPE after placebo was 19, median IELT after placebo was 60 s and median male SQOL after placebo was 21. Paired comparison of AIPE, IELT (Secs), inter quartile range (IQR) and male SQOL in group (A) patients at baseline and after duloxetine intake showed statistically significant improvement among treated patients (p values < 0.001 for all). Paired comparison of AIPE, IELT (Secs), IQR and male SQOL in group (A) patients at baseline and after placebo treatment showed no significant improvement of male SQOL. Furthermore, AIPE and IELT returned to baseline scores after discontinuation of duloxetine (p values 0.729; 0.892, respectively). Paired comparison of AIPE, IELT (Secs), IQR and male SQOL in group (B) patients at baseline and after placebo treatment showed almost same scores of patients in group (A) who received placebo for 2 months after a 2 month washout period (p values 1.000 for all). Paired comparison of AIPE, IELT (Secs), IQR and male SQOL in group (B) patients at baseline and after duloxetine treatment showed statistically significant improvement among all treated patients (p values < 0.001 for all). CONCLUSION: Duloxetine is an effective drug for treatment of LPE and APE patients. Further, larger studies are needed to compare duloxetine to different known therapeutic modalities for PE to assert it's efficacy and superiority.


RéSUMé: CONTEXTE: L'éjaculation précoce (EP) est considérée comme le trouble sexuel masculin le plus courant, touchant 20% à 66% des hommes sexuellement actifs. La plupart des patients avaient déjà essayé la dapoxitine à la demande sans amélioration. Dans la présente étude, nous avons cherché à déterminer l'efficacité et l'innocuité de l'apport quotidien de 30 mg de duloxétine comme traitement de patients atteints d'éjaculation précoce de longue durée et de patients atteints d'éjaculation précoce acquise. RéSULTATS: La présente étude a montré une amélioration significative du temps de latence éjaculatoire intravaginal (IELT) après la prise de duloxétine. Tous les participants avaient un indice médian de l'éjaculation précoce (AIPE) de 26, un IELT médian de 180 secondes, et une médiane de la qualité de vie sexuelle masculine (SQOL) de 43 après avoir été traités par la duloxétine (p < 0,001 pour tous). Après placebo, l'AIPE médian était de 19, l'IELT médian de 60 secondes et la médiane de la SQOL masculine de 21. La comparaison appariée de l'AIPE, de l'IELT, de l'intervalle interquartile (IQR) et de la SQOL masculine chez les patients du groupe (A) au départ et après la prise de duloxétine a montré une amélioration statistiquement significative chez les patients traités (p < 0,001 pour tous). La comparaison appariée de l'AIPE, de l'IELT, de l'IQR et de la SQOL masculine chez les patients du groupe (A) au départ et après traitement par placebo n'a montré aucune amélioration significative de la SQOL masculine. De plus, l'AIPE et l'IELT sont revenus aux scores de base après l'arrêt de la duloxétine (respectivement p 0,729; 0,892). La comparaison appariée de l'AIPE, de l'IELT, de l'IQR et de la SQOL masculine chez les patients du groupe (B) au départ et après traitement par placebo a montré presque les mêmes scores que les patients du groupe (A) qui ont reçu un placebo pendant 2 mois après une période de sevrage thérapeutique de 2 mois (p 1,000 pour tous). La comparaison appariée de l'AIPE, de l'IELT, de l'IQR et de la SQOL masculine chez les patients du groupe (B) au départ et après le traitement par la duloxétine a montré une amélioration statistiquement significative chez tous les patients traités (p < 0,001 pour tous). CONCLUSIONS: La duloxétine est un médicament efficace pour traiter des patients atteints d'éjaculation précoce de longue durée, et ceux atteints d'éjaculation précoce acquise. D'autres études de plus grande envergure sont nécessaires pour comparer la duloxétine aux différentes modalités thérapeutiques connues de l'éjaculation précoce, afin de déterminer son efficacité et sa supériorité. MOTS-CLéS: Ejaculation précoce de longue Durée; Ejaculation précoce acquise; Duloxétine; Qualité de Vie sexuelle masculine.

10.
Sci Rep ; 13(1): 14673, 2023 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-37673929

RESUMO

Cryptides are a subfamily of bioactive peptides that exist in all living organisms. They are latently encrypted in their parent sequences and exhibit a wide range of biological activities when decrypted via in vivo or in vitro proteases. Cationic cryptides tend to be drawn to the negatively charged membranes of microbial and cancer cells, causing cell death through various mechanisms. This makes them promising candidates for alternative antimicrobial and anti-cancer therapies, as their mechanism of action is independent of gene mutations. In the current study, we employed an in silico approach to identify novel cationic cryptides with potential antimicrobial and anti-cancer activities in atypical and systematic strategy by reanalysis of a publicly available RNA-seq dataset of Pacific white shrimp (Penaus vannamei) in response to bacterial infection. Out of 12 cryptides identified, five were selected based on their net charges and potential for cell penetration. Following chemical synthesis, the cryptides were assayed in vitro to test for their biological activities. All five cryptides demonstrated a wide range of selective activity against the tested microbial and cancer cells, their anti-biofilm activities against mature biofilms, and their ability to interact with Gram-positive and negative bacterial membranes. Our research provides a framework for a comprehensive analysis of transcriptomes in various organisms to uncover novel bioactive cationic cryptides. This represents a significant step forward in combating the crisis of multi-drug-resistant microbial and cancer cells, as these cryptides neither induce mutations nor are influenced by mutations in the cells they target.


Assuntos
Anti-Infecciosos , Neoplasias , Penaeidae , Animais , Anti-Infecciosos/farmacologia , Neoplasias/tratamento farmacológico , Biofilmes , Bioensaio , Cátions
11.
Sci Rep ; 13(1): 1275, 2023 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-36690671

RESUMO

A comprehensive study was carried out on in vitro multiplication and rooting using the medium enriched with different plant growth regulators and acclimatization of pineapple cv. 'Smooth Cayenne' using different soil growing substrates. The significantly highest shoot buds (Avg. 16.7) were obtained on the medium comprising 2.0 mg L-1 BA (6-Benzylaminopurine). Results showed that 1.0 mg L-1 IBA (Indole-3-butyric acid) increased the thickness and length of white adventitious roots and resulted in a significantly highest number of roots (Avg. 8) and root length (6.15 cm). Plantlets with healthy, multiple roots were transplanted in several soil combinations of river silt, bolhari (yellow sand), and peat moss. However, the significantly highest survival (100%) of plantlets in the greenhouse was obtained on the soil medium containing only peat moss. Furthermore, soil mixtures of bolhari and peat moss (1:1) and river silt alone exhibited 98.9% and 95.1% survivability of plantlets, which was also considered equally significant (at 5% probability level). The in vitro and ex vitro protocols optimized in the current study can be applied commercially for pineapple crop worldwide.


Assuntos
Ananas , Solo , Brotos de Planta , Nutrientes , Aclimatação
12.
bioRxiv ; 2023 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-38187734

RESUMO

Breast-cancer brain metastasis (BCBM) poses a significant clinical challenge, resulting in an end-stage diagnosis and hindered by limited therapeutic options. The blood-brain barrier (BBB) acts as an anatomical and physiological hurdle for therapeutic compounds, restricting the effective delivery of therapies to the brain. In order to grow and survive in a nutrient-poor environment, tumors in the brain must adapt to their metabolic needs, becoming highly dependent on acetate. These tumors rely on the conversion of acetate to acetyl-CoA by the enzyme Acetyl-CoA synthetase 2 (ACSS2), a key metabolic enzyme involved in regulating fatty acid synthesis and protein acetylation in tumor cells. ACSS2 has emerged as a crucial enzyme required for the growth of tumors in the brain. Here, we utilized a computational pipeline, combining pharmacophore-based shape screen methodology with ADME property predictions to identify novel brain-permeable ACSS2 inhibitors. From a small molecule library, this approach identified 30 potential ACSS2 binders, from which two candidates, AD-5584 and AD-8007, were validated for their binding affinity, predicted metabolic stability, and, notably, their ability to traverse the BBB. We show that treatment of BCBM cells, MDA-MB-231BR, with AD-5584 and AD-8007 leads to a significant reduction in lipid storage, reduction in colony formation, and increase in cell death in vitro . Utilizing an ex vivo orthotopic brain-slice tumor model, we show that treatment with AD-8007 and AD-5584 significantly reduces tumor size and synergizes with radiation in blocking BCBM tumor growth ex vivo. Importantly, we show that following intraperitoneal injections with AD-5584 and AD-8007, we can detect these compounds in the brain, confirming their BBB permeability. Thus, we have identified and validated novel ACSS2 inhibitor candidates for further drug development and optimization as agents for treating patients with breast cancer brain metastasis.

13.
Schizophr Res Cogn ; 27: 100214, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34557386

RESUMO

BACKGROUND: Despite fast progress in neuroscientific approaches, the neurobiological continuum links psychotic spectrum, and affective disorder is obscure. White matter WM abnormalities found utilizing Diffusion Tensor Imaging (DTI) showing impaired communication in both disorders have been consistently demonstrated; however, direct comparisons of findings between them are scarce. This study aims to study WM abnormalities in single episode bipolar I disorder, and single episode brief psychotic disorder related to healthy control with the association of executive function. METHODS: A cross-sectional case-control study was used to assess 60 subjects divided into 20 patients with single episode bipolar I disorder, 20 individuals with single episode brief psychotic disorder (both groups of patients were in remission), and 20 healthy controls. The present study examined the superior longitudinal fasciculus (SLF), and cingulum bundle fractional anisotropy (FA) determined from DTI images symmetrically and connected these results with cognitive functions as assessed by the trail making test (TMT) and Wisconsin card sorting test (WCST). RESULTS: DTI data indicated that the psychotic group had a significant decrease in FA of the right SLF (p-value less than 0.001), left SLF (p-value less than 0.001), and left cingulum (p-value less than 0.001) than the bipolar I group. In terms of executive functioning, the psychotic group performed significantly worse than the bipolar I group on the TMT part B (p-value less than 0.001), the WCST (number of classifications fulfilled) (p-value less than 0.001), and perseverative errors (p-value less than 0.001). CONCLUSION: Even after clinical remission, individuals with single episode brief psychotic disorder had more pronounced white matter impairments and executive function deficiencies than individuals with single episode bipolar I disorder.

14.
Reprod Sci ; 29(6): 1836-1843, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35359224

RESUMO

We aimed to find a correlation between the intraoperative diameters of the seminiferous tubules evaluated at high magnification during micro-testicular sperm extraction (micro-TESE) and total motile sperm count (TMSC) in non-obstructive azoospermic (NOA) patients. Five hundred four consecutive NOA patients were included and underwent micro-TESE. The change in the mean TMSC and different seminiferous tubular diameters was of high statistical significance (p < 0.001). It should be noted that the highest mean TMSC was reported in the dilated tubules (DTs) group followed by the other study groups 941.72 ± 196.97, 487.37 ± 443.57, and 34.54 ± 60.79, respectively. Furthermore, 21 naïve cases had dilated tubules (DTs) and 18 (85.7%) of them had shown eventful micro-TESE. Conversely, 186 naïve cases had slightly dilated tubules (SDTs), and 101 (54.3%) of them had eventful micro-TESE. Only 8 (24.25%) cases of the 33 cases had non dilated tubules (NDTs) and showed eventful micro-TESE. The frequency of intrasurgical seminiferous tubular diameter and micro-TESE outcome among the naïve cases had demonstrated a highly statistical significance (p < 0.001). Interestingly, all salvaged cases (100%) with DTs and a previous eventful TESE had shown eventful TESE in the current study. The most dilated intrasurgical seminiferous tubular diameter is associated with the highest TMSC in NOA patients including SCO cases.


Assuntos
Azoospermia , Azoospermia/cirurgia , Humanos , Masculino , Estudos Prospectivos , Estudos Retrospectivos , Contagem de Espermatozoides , Recuperação Espermática , Espermatozoides , Testículo
15.
Int J Telemed Appl ; 2022: 3811068, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35313723

RESUMO

Incorporation of telemedicine in general clinical practice is becoming a compelling need nowadays in the context of COVID-19 pandemic and its consequent burdens on the healthcare systems. Though telemedicine appears to be appealing and carries a lot of advantages, yet it is still faced by many challenges and barriers especially in developing countries. Our aim was to explore the impression of healthcare providers about telemedicine and its applicability in clinical practice in Egypt. A cross-sectional study was conducted among healthcare providers from different Egyptian governorates through a web-based survey. The survey gathered information about demographic, socioeconomic features of the enrolled healthcare participants; their knowledge, previous experience, impression about telemedicine, advantages of telemedicine over traditional medical services, barriers that may face telemedicine, and additional services that can be provided by telemedicine were also explored. Our study enrolled 642 healthcare providers from all over Egypt, 43.77% were females, of which 55.5% were physicians, 27.3% were nurses, 6.1% were technicians, 7.6% were administrative clerks, and 3.6% were medical directors. Sixty-four percent of participants reported that they have never used telemedicine. Smartphones were the most commonly used mean in the group who used telemedicine (65%), and smartphone applications were the favorable telemedicine service for about 50% of participants. Participants assumed that the use of telemedicine might not have a negative effect on the doctor-patient relationship but raised some concerns regarding the privacy and security of patients' data. Despite the fact that telemedicine appears to be appealing and widely accepted by healthcare providers, yet still, its implementation is confronted by some obstacles. Precise organizational guidelines need to be developed to clearly figure out the exact role of each healthcare provider to minimize their doubtfulness about telemedicine and to facilitate its adoption.

16.
Bull Natl Res Cent ; 45(1): 39, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33584092

RESUMO

BACKGROUND: COVID-19 (Corona Virus Disease 2019) is showing a wide global spread, and urgent joint international efforts is required to the control of this pandemic, the awareness of people towards infectious viruses still the main factor to limit the widespread of disease. The aim of this study is to assess the level of awareness and attitude towards COVID-19 among a sample of Egyptian school children, using a web-based questionnaire. RESULTS: A total of 708 participants were involved in this online survey study, representing different areas in Egypt, 378 males (53.4%), 330 females (46.5%); their age range between 6 and 18 years. Regarding the residence, 576 (81.4%) were from urban areas, the remaining 132 (18.6%) were from non-urban areas. Internet and media were more frequent used as a source of information in urban students. The knowledge level score of risk and prevention of the disease were significantly higher in urban students than in non-urban students. Healthy practice score ≥ 50 were significantly more frequent in urban students. Healthy practice score was non-significantly higher in urban students. CONCLUSIONS: Most of the study participants of school students are knowledgeable about basic information, and have cautious preventive practices towards COVID-19, denoting the efficacy of the public health efforts. However, the lower level of awareness in non-urbans, indicating a need to address alternative channels to communicate with these populations.

17.
ACS Chem Biol ; 16(1): 193-204, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33410670

RESUMO

A strategy has been established for the synthesis of a family of bifunctional HIV-1 inhibitor covalent conjugates with the potential to bind simultaneously to both the gp120 and gp41 subunits of the HIV-1 envelope glycoprotein trimeric complex (Env). One component of the conjugates is derived from BNM-III-170, a small-molecule CD4 mimic that binds to gp120. The second component, comprised of the peptide DKWASLWNW ("Trp3"), was derived from the N-terminus of the HIV-1 gp41 Membrane Proximal External Region (MPER) and found previously to bind to the gp41 subunit of Env. The resulting bifunctional conjugates were shown to inhibit virus cell infection with low micromolar potency and to induce lysis of the HIV-1 virion. Crucially, virolysis was found to be dependent on the covalent linkage of the BNM-III-170 and Trp3 domains, as coadministration of a mixture of the un-cross-linked components proved to be nonlytic. However, a significant magnitude of lytic activity was observed in Env-negative and other control pseudoviruses, suggesting parallel mechanisms of action of the conjugates involving Env interaction and direct membrane disruption. Computational modeling suggested strong membrane-binding activity of BNM-III-170, which may underly the nonspecific virolytic effects of the conjugates. To investigate the scope of the membrane effect, cell-based cytotoxicity and membrane permeability assays were performed employing flow cytometry. Here, we observed a dose-dependent and specific cytotoxic effect on HIV-1 Env-expressing cells by the small-molecule bifunctional inhibitor. Most importantly, Env-negative cells were not susceptible to the cytotoxic effect upon exposure to this construct at concentrations where cell-killing effects were observed for Env-positive cells. Computational structural modeling supports a mechanism in which the bifunctional inhibitors bind to the gp120 and gp41 subunits in tandem in open-state Env trimers and induce relative motion of the gp120 subunits consistent with models of Env inactivation. This observation supports the idea that the cell-killing effect of the small-molecule bifunctional inhibitor is due to specific Env conformational triggering. This work lays important groundwork to advance a small-molecule bifunctional inhibitor approach for eliminating Env-expressing infected cells and the eradication of HIV-1.


Assuntos
Morte Celular/efeitos dos fármacos , Proteína gp120 do Envelope de HIV/metabolismo , Proteína gp41 do Envelope de HIV/metabolismo , HIV-1/metabolismo , Peptídeos/farmacologia , Bibliotecas de Moléculas Pequenas/farmacologia , Peptídeos/química , Bibliotecas de Moléculas Pequenas/química
18.
Environ Sci Pollut Res Int ; 27(2): 1776-1788, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31758477

RESUMO

This is the first nationwide survey of bisphenol A (BPA), methylparaben, ethylparaben, propylparaben, butylparaben, and o-phenylphenol, in Egypt's water. Five hundred fifty-five water samples were collected from source water (SW, 109 samples) and drinking water (DW, 446 samples) of twenty-three Egyptian governorates. These chemicals were determined by direct ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis of a filtered aliquot of samples. The impacts of the measured concentrations on the aquatic organisms and human health were evaluated as well. BPA, methylparaben, propylparaben, and butylparaben were frequently detected in SW and DW, while ethylparaben and o-phenylphenol were not detected whatsoever. The most frequently detected endocrine-disrupting chemical (EDC) was BPA in SW and methylparaben in DW. The recorded highest concentrations of BPA and methylparaben in SW and BPA and methylparaben, propylparaben, and butylparaben in DW were the highest worldwide. Of the investigated twenty-three governorates, the SW and DW of Aswan, Red Sea, Cairo, Sharqia, and Damietta were free of the studied EDCs. Contrarily, BPA, MeP, PrP, and BuP were detected in Sohag's SW and DW. A detection ratio > 70% was recorded in SW of Faiyum, Dakahlia, and Ismailia, and > 90% in DW of Sohag, Port Said, Dakahlia, and Faiyum. The environmental risk assessment results excluded any human health risk even in the worst-case scenario and showed that BPA represents the highest risk to the aquatic organisms.


Assuntos
Água Potável/análise , Disruptores Endócrinos/análise , Poluentes Químicos da Água/análise , Cromatografia Líquida , Egito , Monitoramento Ambiental , Humanos , Medição de Risco , Espectrometria de Massas em Tandem
19.
Biol Trace Elem Res ; 194(1): 135-144, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31066019

RESUMO

This study is aimed at evaluating the effect of dietary zinc-methionine (Zn-Met) supplementation during 3 months prepartum up to 9 months postpartum on reproductive performance, blood biochemical, and milk production of lactating she-camels besides growth performance of their calves. Twenty pregnant Maghrebi she-camels (439.49 ± 11.57 kg; 3-5 parties) were divided into four similar groups. Animals were fed the basal diet (G1) or the basal diet supplemented with Zn-Met at levels of 30 mg (G2), 40 mg (G3), and 50 mg (G4)/kg diet. Results revealed that IgA, IgM, and IgG concentrations in colostrum, monthly milk yield, and lactation period were significantly increased in Zn-Met-supplemented groups. Milk contents of fat, ash, and total solids improved (P < 0.05) in G4 as compared with other groups. Pre- and postpartum Zn, T3, T4, P4, and E2 concentrations in plasma and milk Zn level were higher (P < 0.05) in all Zn-Met-supplemented groups. Postpartum first estrus interval, number of services/conception, days open, pregnancy rate, duration of placental drop, and calving interval improved (P < 0.05) in G4. Weaning weight and average daily gain of calves were enhanced all in Zn-Met-supplemented groups. Conclusively, the inclusion of Zn-Met especially at a level of 50 mg/kg diet, 3 months prepartum up to 9 months postpartum, led to better productive and reproductive performance, immunity of she-camels, and growth performance of their offspring.


Assuntos
Suplementos Nutricionais , Metionina/farmacologia , Leite/efeitos dos fármacos , Prenhez , Reprodução/efeitos dos fármacos , Zinco/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Camelus , Feminino , Metionina/administração & dosagem , Metionina/sangue , Gravidez , Zinco/administração & dosagem , Zinco/sangue
20.
Vet Res Forum ; 11(3): 219-227, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33133458

RESUMO

This study was performed to evaluate the efficacy of two levels of dietary oregano essential oil (OEO) on growth performances, biochemical, hematological parameters, and intestinal histomorphology in Japanese quail. A total number of 99 quail chicks were divided into three groups (33 quails per group): Control, OEO 150 mg kg-1, and OEO 300 mg kg-1 treated groups for 42 days. Feed conversion ratio (FCR), feed intake, weight gain, and edible organ weight were recorded. Biochemical and hematological parameters were determined. Histomorphological examination of hepatic and intestinal tissues was performed. FCR was significantly improved and feed intake was significantly decreased in OEO 150 mg kg-1 group compared to control. No detectable changes were observed in the lipid profile. Meanwhile, total protein, albumin, globulin, and H/L ratio were significantly increased in OEO 300 mg kg-1 at day 21. Uric acid and creatinine were significantly increased in the OEO 300 mg kg-1 group at day 42. A significant increase was observed in the whole thickness of the small intestine in the OEO 150 mg kg-1 group besides a significant increase in villi length, width, and crypt depth. Vacuolar and fatty degeneration of the hepatocytes along with Kupffer cell hypertrophy was observed in OEO 300 mg kg-1 group. It was concluded that OEO 150 mg kg-1 improved the quail's performance, intestinal histomorphometry as well as hematological parameters with no negative impacts on biochemical parameters.

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